Cyclodextrins are cyclic molecules consisting of 1-4 linked alpha-D-glucopyranose monomeric units. The cyclodextrins containing 6-, 7-, and 8-glucose units joined to form a ring, commonly known as alpha-, beta-, and gamma-cyclodextrin, respectively, are the most important cyclodextrins to date, possibly because of their availability relative to cyclodextrins of different ring size. The usefulness of these cyclodextrins arises from their ability to reversibly form inclusion complexes, or clathrates, with many types of compounds. Inclusion complexes arise when a host molecule, such as a cyclodextrin, has a structure containing an interior cavity into which guest molecules can bind by weak interactions such as van der Waal's forces. The latter are short range forces which are sufficiently strong to allow the formation of definite, generally solid complexes, but are sufficiently weak to permit ready dissociation of the complex to a host and guest molecule under appropriate conditions.
The cyclodextrins are doughnut-shaped molecules with an interior cavity whose size and shape is determined by the number of glucose units that make up the ring. In alpha-cyclodextrin the almost cylindrical cavity is approximately 7 angstroms deep and 5 angstroms in diameter. In beta-cyclodextrin the depth is the same but the diameter is 7 angstroms, and in gamma-cyclodextrin cavity is again 7 angstroms deep but is 9 angstroms in diameter. Cyclodextrins are soluble in water because of the many hydroxyl groups of the glucose subunits that surround the rim of the cavity. However, the interior of the cavities themselves is hydrophobic, and these hydrophobic cavitives extract organic molecules from aqueous solution if the organic materials have the correct shape and hydrophobic character.
The complexing ability of cyclodextrins lends itself to various uses. For example, the cyclodextrins are used in encapsulating desirable flavors and fragrances which can then be stored for reasonably long periods of time and added to foods at their preparation. Reciprocally, cyclodextrins may be used in removing undesirable flavors and fragrances from food by complexing with them. Cyclodextrins also are used in the protection of foods against oxidation, photochemical degradation, and thermal decomposition. These and other uses have been summarized by J. Szejtli, Starch, 34, 379-385 (1982)
Although in some applications the use of the water soluble cyclodextrins themselves are appropriate, in other cases it is more desirable to employ an insolubilized cyclodextrin to more readily enable its extended use or to enable its incorporation in a continuous process. For example, when cyclodextrins are employed for their ability to separate various components, as in gas phase chromatography or high pressure liquid chromatography, the water soluble cyclodextrins have obvious limitations and some sort of solid phase incorporating cyclodextrins is needed. Another example is the use of cyclodextrins to removed bitter components in citrus juice where it is desired to pass the juice over a solid bed incorporating cyclodextrins to give an effluent of reduced bitterness.
These needs previously have been recognized, and one general solution is the preparation of polymeric cyclodextrin derivatives as resins having properties appropriate for a solid support in chromatographic applications or for use as a fixed bed in continuous processes. Buckler et al. in U.S. Pat. No. 3,472,835 recognized the need for insolubilized cyclodextrins as "molecular sieves" in the separation and purification processes and offered as a general solution insoluble derivatives prepared from the reaction of cyclodextrins with compounds having at least two hydroxyl-reactive functional groups per molecule. The patentee disclosed a large class of suitable polyfunctional compounds, including dicarboxylic acid dihalides, and exemplified several insoluble polymeric cyclodextrin derivatives suitable for use in numerous described applications.
The limited porosity of such prior art resins impedes the diffusivity of guest molecules and seriously curtails the capacity of the resin to bind with typical guest molecules, both of which are marked disadvantages. It was reasoned that increasing the effective porosity of the insolubilized cyclodextrins prepared by crosslinking cyclodextrin with dicarboxylic acid dihalides could increase their binding kinetics and their discrimination, substantially improving the utility in commercial processes. In particular, it appeared that if a thin film of an insolubilized cyclodextrin were supported on a porous refractory inorganic oxide with retention of at least a major part of the cyclodextrin's complexing selectivity, not only might the mass transport limitations of a non-porous, unsupported solid resin be overcome, at least in part, but the supported resin would have good flow characteristics, high incompressibility, crush strength, and abrasion resistance, all desirable characteristics for material used in a fixed or packed bed. The invention to be described pertains to such supported insolubilized cyclodextrins where the cyclodextrin is crosslinked by dicarboxylic acid dihalides on the surface of a porous refractory inorganic oxide. The increase in porosity affords a product with improved kinetics of guest molecule inclusion and greater selectivity relative to discrete resin particles.